Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis.
In this study, we determined conditions leading to the development of colitis in mice with nucleotide binding oligomerization domain 2 (NOD2) deficiency, a susceptibility factor in Crohn's disease. We found that NOD2-deficient antigen-presenting cells (APCs) produced increased amounts of interleukin (IL)-12 in the presence of ovalbumin ( OVA) peptide and peptidoglycan or recombinant E. coli that express OVA peptide (ECOVA). Furthermore, these APCs elicited heightened interferon-gamma ( IFN-gamma) responses from cocultured OVA-specific CD4(+) T cells. We then demonstrated that NOD2-deficient mice adoptively transferred OVA-specific CD4(+) T cells and that administered intrarectal ECOVA developed colitis associated with the expansion of OVA-specific CD4(+) T cells producing IFN-gamma. Importantly, this colitis was highly dependent on Toll-like receptor 2 ( TLR2) function since it was suppressed in NOD2 and TLR2 double-deficient mice. Thus, NOD2-deficient mice become susceptible to colitis as a result of increased TLR2 responses when they have the capacity to respond to an antigen expressed by mucosal bacteria.[1]References
- Nucleotide Binding Oligomerization Domain 2 Deficiency Leads to Dysregulated TLR2 Signaling and Induction of Antigen-Specific Colitis. Watanabe, T., Kitani, A., Murray, P.J., Wakatsuki, Y., Fuss, I.J., Strober, W. Immunity (2006) [Pubmed]
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